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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxygen diffusion in plasma membranes and mitochondrial (Mt) membranes of ventricular myocytes isolated from adult rat hearts was measured using O2-induced fluorescence quenching of pyrene-butyric acid. The diffusion coefficient for oxygen (DO2 in 10(-6).cm2 x s-1) of the plasma membrane was 2.91 +/- 0.05 (37 degrees C) in the control group, which was significantly higher than that of Mt membrane (2.23 +/- 0.11) (P < 0.001). The DO2 of the plasma membrane was reduced to 2.50 +/- 0.08 (P < 0.001) in myocytes isolated from heart after 15 min reperfusion following no-flow ischemia for 30 min, while that of the Mt membrane remained almost unchanged. Administration of hydrogen peroxide and hypochlorous acid to the isolated myocytes also reduced the plasma membrane DO2. The decrease in the plasma membrane DO2 correlated with that in the fraction of rod-shaped myocytes. We conclude that the plasma membrane is more susceptible to reperfusion injury than the Mt membrane, but these membranes do not limit O2 uptake in the heart because of the high absolute values of DO2.
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PMID:Diffusion coefficient for O2 in plasma and mitochondrial membranes of rat cardiomyocytes. 133 8

Intrinsic mechanisms of vasodilatation may prevent injury-related ischemia in peripheral nerve endoneurium. We examined local perfusion up to 10 days following local crush, partial injury or simple exposure of the rat sciatic nerve. By employing epineurial hCGRP(8-37), a receptor antagonist of CGRP, and serial hydrogen clearance measurements, we estimated the component of post-injury blood flow related to local CGRP action. Injury-related ischemia was not observed at any of the time points studied at or proximal to injury. Instead, endoneurial blood flow (EBF) increased at 24 h proximal to crush or partial injury, and at 48 h within the crush zone when compared to sham operated controls or to a pooled reference range of EBF. Composite blood flow (F) was also elevated at 48 h and 5 days within the crush zone suggesting hyperemia involving the epineurial plexus, perineurial vessels and AV shunts. hCGRP(8-37) constricted vasa nervorum at most time points but its effect on EBF was maximum and exceeded controls within the crush zone at 48 h. The findings indicate that certain types of nerve injury, including focal crush, are associated with hyperemia, not ischemia. CGRP vasodilatation may account for part of this response, implying a local peptidergic afferent fiber response to nerve trunk injury.
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PMID:Hyperemia of injured peripheral nerve: sensitivity to CGRP antagonism. 133 7

Ischemic glutamate excitotoxicity may be counteracted by adenosine which appears extracellularly during ischemia as an intermediate purine catabolite and has the potential to modulate glutamate release and its receptor action. The present study was conducted to evaluate the flow threshold for purine catabolite accumulation in relation to that for glutamate elevation in focal ischemia which was induced by middle cerebral artery (MCA) occlusion in halothane anesthetized cats. Assemblies of platinum electrodes and microdialysis probes were inserted into the somatosensory (SF, n = 13) and the auditory (A, n = 9) cortices to assess local cerebral blood flow (CBF) using hydrogen clearance and purine catabolite (adenosine, inosine and hypoxanthine) as well as glutamate concentrations in the dialysate using high-performance liquid chromatography (HPLC). In both investigated areas, purine catabolites were elevated if CBF fell below 25 ml/100 g/min, while glutamate increased at a flow threshold below 20 ml/100 g/min. Maximum elevations of adenosine, inosine and hypoxanthine were 76-, 29- and 11-fold, respectively, that of glutamate was 24-fold. In the range between 20 and 25 ml/100 g/min, significant increases of adenosine (5-15-fold) were measured, while glutamate did not markedly increase. The elevation of adenosine was transient whereas that of inosine, hypoxanthine and glutamate persisted over an ischemic period of 3 h. The higher flow threshold for adenosine may reflect an inherent but time limited protective mechanism against glutamate excitotoxicity.
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PMID:Flow thresholds for extracellular purine catabolite elevation in cat focal ischemia. 135 28

Biosynthesis of the polyamines spermidine and spermine and their precursor putrescine is controlled by the activity of the two key enzymes ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC). In the adult brain, polyamine synthesis is activated by a variety of physiological and pathological stimuli, resulting most prominently in an increase in ODC activity and putrescine levels. The sharp rise in putrescine levels observed following severe cellular stress is most probably the result of an increase in ODC activity and decrease in SAMDC activity or an activation of the interconversion of spermidine into putrescine via the enzymes spermidine N-acetyltransferase and polyamine oxidase. Spermidine and spermine levels are usually less affected by stress and are reduced in severely injured areas. Changes of polyamine synthesis and metabolism are most pronounced in those pathological conditions that induce cell injury, such as severe metabolic stress, exposure to neurotoxins or seizure. Putrescine levels correlate closely with the density of cell necrosis. Because of the close relationship between the extent of post-stress changes in polyamine metabolism and density of cellular injury, it has been suggested that polyamines play a role in the manifestation of structural defects. Four different mechanisms of polyamine-dependent cell injury are plausible: (1) an overactivation of calcium fluxes and neurotransmitter release in areas with an overshoot in putrescine formation; (2) disturbances of the calcium homeostasis resulting from an impairment of the calcium buffering capacity of mitochondria in regions in which spermine levels are reduced; (3) an overactivation of the NMDA receptor complex caused by a release of polyamines into the extracellular space during ischemia or after ischemia and prolonged recirculation in the tissue surrounding severely damaged areas; (4) an overproduction of hydrogen peroxide resulting from an activation of the interconversion of spermidine into putrescine via the enzymes spermidine N-acetyltransferase and polyamine oxidase. Insofar as a sharp activation of polyamine synthesis is a common response to a variety of physiological and pathological stimuli, studying stress-induced changes in polyamine synthesis and metabolism may help to elucidate the molecular mechanisms involved in the development of cell injury induced by severe stress.
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PMID:Polyamine metabolism in different pathological states of the brain. 135 85

Radicals are species containing one or more unpaired electrons, such as nitric oxide (NO.). The oxygen radical superoxide (O2.-) and the nonradical hydrogen peroxide (H2O2) are produced during normal metabolism and perform several useful functions. Excessive production of O2.- and H2O2 can result in tissue damage, which often involves generation of highly reactive hydroxyl radical (.OH) and other oxidants in the presence of "catalytic" iron or copper ions. An important form of antioxidant defense is the storage and transport of iron and copper ions in forms that will not catalyze formation of reactive radicals. Tissue injury, e.g., by ischemia or trauma, can cause increased metal ion availability and accelerate free radical reactions. This may be especially important in the brain because areas of this organ are rich in iron and CSF cannot bind released iron ions. Oxidative stress on nervous tissue can produce damage by several interacting mechanisms, including increases in intracellular free Ca2+ and, possibly, release of excitatory amino acids. Recent suggestions that free radical reactions are involved in the neurotoxicity of aluminum and in damage to the substantia nigra in patients with Parkinson's disease are reviewed. Finally, the nature of antioxidants is discussed, it being suggested that antioxidant enzymes and chelators of transition metal ions may be more generally useful protective agents than chain-breaking antioxidants. Careful precautions must be used in the design of antioxidants for therapeutic use.
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PMID:Reactive oxygen species and the central nervous system. 140 8

Cerebral monoaminergic neurotransmitters and their metabolites show various concentration changes in gerbils following bilateral carotid ligation. The present study evaluated the effect of chronic administrations of lisuride hydrogen maleate (lisuride) on these changes. Lisuride (0.01 mg/kg or 0.05 mg/kg) or vehicle was intraperitoneally administered to gerbils for 14 consecutive days before the induction of a 30 min ischemia by bilateral carotid ligation. Animals were sacrified immediately and the levels of dopamine, DOPAC, homovanillic acid, noradrenaline, serotonin and 5-hydroxyindoleacetic acid determined by HPLC in the striatum, cortex, hippocampus and diencephalon/midbrain. Lisuride itself had no effect on any compound determined in any region. In the carotid-ligated gerbil brain, however, lisuride corrected the reduction of dopamine in the striatum, normalized or reduced increases in the (DOPAC+homovanillic acid)/dopamine ratio in the striatum, hippocampus and diencephalon/midbrain, and increased the levels of serotonin in all four regions. The present study, together with previous reports, indicate that lisuride may interfere with ischemia-induced cerebrovascular disturbances and, in such a way, improve some pathological sequelae of cerebrovascular disease.
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PMID:Effects of chronic administration of lisuride hydrogen maleate on aromatic amine and metabolite levels in the gerbil brain following bilateral common carotid ligation. 141 64

A striking similarity exists between the pathogenetic properties of group A streptococci and those of activated mammalian professional phagocytes (neutrophils, macrophages). Both types of cells are endowed by the ability to adhere to target cells; to elaborate oxidants, hydrolases, and membrane-active agents (hemolysins, phospholipases); and to freely invade tissues and destroy cells. From the evolutionary point of view, streptococci might justifiably be considered the forefathers of "modern" leukocytes. Our earlier findings that synergy between a streptococcal hemolysin (streptolysin S, SLS) and a streptococcal thiol-dependent proteinase and between cytotoxic antibodies+complement and streptokinase-activated plasmin readily killed tumor cells, led us to hypothesize that by analogy to the pathogenetic mechanisms of streptococci, the mechanisms of tissue destruction initiated by activated leukocytes in inflammatory sites, as well as in tissues undergoing episodes of ischemia and reperfusion, might also be the result of the synergistic effects among leukocyte-derived oxidants, phospholipases, proteinases, cytokines, and cationic proteins. The current report extends our previous synergy studies with endothelial cells to two additional cell types--monkey kidney epithelial cells and rat beating heart cells. Monolayers of 51Cr-labeled cells that had been treated by combinations of sublytic amounts of hydrogen peroxide (generated either by glucose oxidase, xanthine-xanthine oxidase, or by paraquat) and with sublytic amounts of a variety of membrane-active agents (streptolysin S, phospholipases A2 and C, lysophosphatides, histone, chlorhexidine) were killed in a synergistic manner (double synergy). Crystalline trypsin markedly enhanced cell killing by combinations of oxidant and the membrane-active agents (triple synergy). Injury to the cells was characterized by the appearance of large membrane blebs that detached from the cells and floated freely in the media, looking like lipid droplets. Cytotoxicity induced by the various combinations of agonists was depressed, to a large extent, by scavengers of hydrogen peroxide (catalase, dimethyl thiourea, and by Mn2+) but not by SOD or by deferoxamine. When cationic agents were employed together with hydrogen peroxide, polyanions (heparin, polyanethole sulfonate) were also found to inhibit cell killing. It is proposed that in order to effectively combat the deleterious toxic effects of leukocyte-derived agonists on cells and tissues, antagonistic "cocktails" comprised of cationized catalase, cationized SOD, dimethylthiourea, Mn(2+)+glycine, proteinase inhibitors, putative inhibitors of phospholipases, and polyanions might be concocted. The current literature on synergistic phenomena pertaining to mechanisms of cell and tissue injury in inflammation is selectively reviewed.
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PMID:Synergism among oxidants, proteinases, phospholipases, microbial hemolysins, cationic proteins, and cytokines. 142 26

The effects of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2- (4,8,12-trimethyltridecyl)-2H-1-benzopyran-6yl-hydrogen phosphate] potassium salt (EPC-K1, CAS 127061-56-7), a new compound for ischemia-reperfusion injuries, on lipid peroxidation and phospholipase A2 activity were studied in vitro using rat brain homogenates and human plasma. EPC-K1 inhibited phospholipase A2 activity in human plasma in a concentration-dependent manner (IC50 = 7.3 x 10(-4) mol/l), whereas a mixture of alpha-tocopherol and ascorbic acid did not exhibit this effect. In rat brain homogenates, EPC-K1 also inhibited lipid peroxidation in a concentration-dependent manner (IC50 = 2.3 x 10(-6) mol/l). alpha-Tocopherol was less active than EPC-K1. These properties of EPC-K1 suggest that EPC-K1 may prove useful in the treatment of ischemia-reperfusion injuries.
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PMID:In vitro studies on the influence of L-ascorbic acid 2-[3,4-dihydro- 2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6yl-hy drogen phosphate] potassium salt on lipid peroxidation and phospholipase A2 activity. 144 71

Endothelin (ET) is a potent vasoconstrictor peptide that may have pathophysiological roles in the microcirculation of the peripheral nervous system. We examined the local action of epineurial ET-1 on sciatic endoneurial blood flow using serial hydrogen clearance measurements in anesthetized, paralyzed, and ventilated Sprague-Dawley rats. In separate rats, we made serial measurements of sciatic motor multifiber conduction before and then after application of epineurial ET (saline on contralateral nerve) 2 and 24 h and 4 and 7 days later. Epineurial bathing solutions of ET increased microvascular resistance and reduced local endoneurial blood flow in a dose-responsive fashion with a half-maximum effective concentration of 10(-8) M. Maximum vasoconstriction at 10(-6) M ET was associated with a fall in endoneurial blood flow from 18.7 (pre-ET) to 7.2 ml x 100 g-1 x min-1. Epineurial norepinephrine (10(-7) to 10(-10) M) also resulted in vasoconstriction, but of lesser degree. Pretreatment with intraperitoneal nimodipine, a dihydropyridine Ca2+ channel antagonist, but not phentolamine, prevented the vasoconstrictive action of ET. Three of eight animals developed temporary but complete axonal conduction block at the site of ET administration (10(-5) M) and four others had partial conduction block. Contralateral saline-treated sciatic fibers were unaffected. Local ET action on extrinsic epineurial microvessels results in reversible ischemia of the underlying endoneurium that may be associated with conduction block. ET's action is more potent than norepinephrine and appears dependent on L-type voltage-gated Ca2+ channels.
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PMID:Acute endoneurial ischemia induced by epineurial endothelin in the rat sciatic nerve. 148 4

Mucosal hemodynamics (by reflectance spectrophotometry) and mucosal damage (by histologic examination) following acute colonic ischemia were evaluated in different anatomic locations in the colon of anesthetized rats. The reflectance spectrophotometer provides an index of mucosal hemoglobin concentration (IHB) and an index of oxygen saturation of hemoglobin (ISO2). The patterns of ischemia without congestion (decreases IHB, decreases ISO2) during superior mesenteric artery occlusion, and ischemia with congestion (increases IHB, decreases ISO2) during portal vein occlusion, previously demonstrated in the stomach and duodenum, are also applicable to the colon. The significant linear correlations between changes (as percent of baseline) in IHB, ISO2, and hydrogen gas clearance suggest that changes in these indices are adequate indicators of changes in colonic mucosal perfusion. Superior mesenteric artery ligation produced significant reductions in both indices, and an increase in damage in the mucosa of the cecum, transverse colon, splenic flexure, and left colon, but not the rectum. Inferior mesenteric artery ligation produced only slight reduction in these indices and minimal damage only in the mucosa of the splenic flexure. These results support the hypothesis that the superior mesenteric artery is more important than the inferior mesenteric artery in maintaining colonic perfusion and colonic mucosal integrity in the rat.
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PMID:Superior mesenteric artery is more important than inferior mesenteric artery in maintaining colonic mucosal perfusion and integrity in rats. 150 83


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